Genomic screening for bipolar disease susceptibility genes using microsatellite markers spaced between 5 to 15 cM apart has been conducted on chromosomes 5, 9, 19, 20 and 21. New markers on chromosomes 7 and 8 and 11p are currently being used for the genotyping. No evidence for linkage, under the assumption of homogeneity, has been found using the lod score method. One locus had a lod score greater than +2 at 0.2 theta. Further analysis of this region with additional markers is being conducted. The scanning of the genome is being extended to regions which were either previously either unmapped or had limited informativeness. We are also using automated genotyping to augment our genome screening through output. A cDNA selection procedure using biotinylated cosmids and primary cDNA is being employed to identify positional candidate genes for bipolar disorder on chromosome 18. Nuclear hormone receptor studies: (With these results the project is phased out). A site critical to the activity of the human glucocorticoid receptor promoter was found corresponding to one of the footprinted regions. AP2 was found to bind to this site and appears to be an important positive regulator for GR expression. A new isoform of human nuclear hormone receptor TR4 was isolated. The A/B region of this gene was found to be encoded by four exons and the gene was mapped to 3p24.2-3pter. New species of the rat TR4 were also identified. The 5' flanking region has an unusual splice site structure.